Onco Pub Date : 2022-03-31 DOI: 10.3390/onco2020005

Nikolaos Dikaios

{"title":"Sparse-Input Neural Networks to Differentiate 32 Primary Cancer Types on the Basis of Somatic Point Mutations","authors":"Nikolaos Dikaios","doi":"10.3390/onco2020005","DOIUrl":"https://doi.org/10.3390/onco2020005","url":null,"abstract":"Background and Objective: This paper aimed to differentiate primary cancer types from primary tumor samples on the basis of somatic point mutations (SPMs). Primary cancer site identification is necessary to perform site-specific and potentially targeted treatment. Current methods such as histopathology and lab tests cannot accurately determine cancer origin, which results in empirical patient treatment and poor survival rates. The availability of large deoxyribonucleic acid sequencing datasets has allowed scientists to examine the ability of somatic mutations to classify primary cancer sites. These datasets are highly sparse since most genes will not be mutated, have a low signal-to-noise ratio, and are often imbalanced since rare cancers have fewer samples. Methods: To overcome these limitations a sparse-input neural network (SPINN) is suggested that projects the input data in a lower-dimensional space, where the more informative genes are used for learning. To train and evaluate SPINN, an extensive dataset for SPM was collected from the cancer genome atlas containing 7624 samples spanning 32 cancer types. Different sampling strategies were performed to balance the dataset. SPINN was further validated on an independent ICGC dataset that contained 226 samples spanning four cancer types. Results and Conclusions: SPINN consistently outperformed classification algorithms such as extreme gradient boosting, deep neural networks, and support vector machines, achieving an accuracy up to 73% on independent testing data. Certain primary cancer types/subtypes (e.g., lung, brain, colon, esophagus, skin, and thyroid) were classified with an F-score > 0.80.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48029223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Akt/mTOR Activation in Lung Cancer Tumorigenic Regulators and Their Potential Value as Biomarkers 肺癌症致瘤调节因子Akt/mTOR的激活及其作为生物标志物的潜在价值

Onco Pub Date : 2022-02-25 DOI: 10.3390/onco2010004

C. Sousa, B. Silva‐Lima, M. Videira

{"title":"Akt/mTOR Activation in Lung Cancer Tumorigenic Regulators and Their Potential Value as Biomarkers","authors":"C. Sousa, B. Silva‐Lima, M. Videira","doi":"10.3390/onco2010004","DOIUrl":"https://doi.org/10.3390/onco2010004","url":null,"abstract":"The high incidence and modest therapeutic outcomes of lung cancer have prompted the identification of cell molecular targets/biomarkers within the complex networks of interactions involved in cell malignancy. Most of the EMT-related regulatory mediators underline patients’ biologic variations, therapeutic refractory events, and tumor cell heterogeneity. Patient stratification based on the understanding of the relevant pathways, such as the PI3K/Akt axis crucial in EMT initiation, could favorably alter disease management. Significant clinical advantage could be expected when overexpressed Akt tyrosine kinase (Akt2) is addressed as a malignant biomarker to guide clinical management decisions, improving prognosis in lung cancer patients. Moreover, one should not miss the opportunity of using it as a druggable target aiming at the inhibition of the downstream complexity that underlies cell proliferation and survival, expression of stemness markers and drug resistance. The value of mTOR, as a downstream target of Akt, and the further activation of EMT transcription factors Twist, Snail and Zeb1 are revisited in this review. An in-depth state-of-the-art assessment provides evidence of its role in the mechanistic inhibition of epithelial markers, such as E-cadherin and miR-200, while inducing the expression of the mesenchymal ones, such as vimentin, N-cadherin, and miR-21. Lastly, evidence suggesting another transcription factor, FOXM1, as the link between the PI3K/Akt and Wnt/β-catenin pathways, prompting cell metabolism through the regulation of p70S6K, is analyzed. A more realistic approach is advised to address unmet clinical needs and support decision making at a clinical level. Taking into consideration several complex intracellular interactions might further improve patient stratification and result in better outcomes.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45967147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Targeting Abnormal Cell Cycle in Cancer: A Preface to the Special Issue 靶向癌症异常细胞周期：特刊序言

Onco Pub Date : 2022-01-13 DOI: 10.3390/onco2010003

Chiaki Takahashi, Jun Kato

引用次数: 0

Optimizing the Pharmacological and Optical Dosimetry for Photodynamic Therapy with Methylene Blue and Nanoliposomal Benzoporphyrin on Pancreatic Cancer Spheroids 优化亚甲基蓝和纳米脂质体苯并卟啉光动力治疗胰腺癌球体的药理学和光学剂量学

Onco Pub Date : 2022-01-07 DOI: 10.3390/onco2010002

Tristan le Clainche, Nazareth Milagros Carigga Gutierrez, Núria Pujol-Solé, J. Coll, M. Broekgaarden

{"title":"Optimizing the Pharmacological and Optical Dosimetry for Photodynamic Therapy with Methylene Blue and Nanoliposomal Benzoporphyrin on Pancreatic Cancer Spheroids","authors":"Tristan le Clainche, Nazareth Milagros Carigga Gutierrez, Núria Pujol-Solé, J. Coll, M. Broekgaarden","doi":"10.3390/onco2010002","DOIUrl":"https://doi.org/10.3390/onco2010002","url":null,"abstract":"Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers are hydrophobic molecules, nanoliposomes are frequently used to increase the biocompatibility of these therapeutics. However, as nanoliposomes can influence the therapeutic performance of photosensitizers, the most suitable treatment parameters need to be elucidated. Here, we evaluate the efficacy of PDT on spheroid cultures of PANC-1 and MIA PaCa-2 pancreatic cancer cells. Two strategies to photosensitize the pancreatic microtumors were selected, based on either nanoliposomal benzoporphyrin derivative (BPD), or non-liposomal methylene blue (MB). Using a comprehensive image-based assay, our findings show that the PDT efficacy manifests in distinct manners for each photosensitizer. Moreover, the efficacy of each photosensitizer is differentially influenced by the photosensitizer dose, the light dose (radiant exposure or fluence in J/cm2), and the dose rate (fluence rate in mW/cm2). Taken together, our findings illustrate that the most suitable light dosimetry for PDT strongly depends on the selected photosensitization strategy. The PDT dose parameters should therefore always be carefully optimized for different models of cancer.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44291543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Core Needle Biopsy Enhances the Activity of the CCL2/CCR2 Pathway in the Microenvironment of Invasive Breast Cancer 核针穿刺增强侵袭性乳腺癌症微环境中CCL2/CCR2通路的活性

Onco Pub Date : 2021-12-30 DOI: 10.3390/onco2010001

M. Heiskala, K. Joensuu, P. Heikkilä

{"title":"Core Needle Biopsy Enhances the Activity of the CCL2/CCR2 Pathway in the Microenvironment of Invasive Breast Cancer","authors":"M. Heiskala, K. Joensuu, P. Heikkilä","doi":"10.3390/onco2010001","DOIUrl":"https://doi.org/10.3390/onco2010001","url":null,"abstract":"The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative biopsies to increase tumor supportive elements in the microenvironment, whereas, in humans, the impact of CNB on the host’s immunologic response has not been investigated. In this pilot study, we compared the expression of CCL2/CCR2 pathway components at the protein level in samples from CNBs to those from the corresponding resected tumors from 52 patients with primary breast cancer. We found an increased expression of CD163, CD14 and CCR2 in monocytes/macrophages and a slight decrease of CCL2 in the malignant epithelium in the tumors after the biopsy. The increased infiltration of immunosuppressive monocytes/macrophages and the decreased tumor cell CCL2 expression, presumably due to the CCR2 availability-dependent CCL2 internalization, suggest that CNB enhances the activity of the CCL2/CCR2 pathway, and this finding warrants confirmatory examination. The switch in the context-dependent role of CCL2 on the polarization of macrophages may lead to increased tumor supportive function both locally and in the peripheral immune machinery. The future directions in breast cancer should include early interventions to support the tumor surveillance of the host.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42382173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Open Data to Support CANCER Science—A Bioinformatics Perspective on Glioma Research 开放数据支持癌症科学——胶质瘤研究的生物信息学视角

Onco Pub Date : 2021-12-13 DOI: 10.3390/onco1020016

Fleur Jeanquartier, Claire Jean-Quartier, Sarah Stryeck, Andreas Holzinger

引用次数: 1

Yttrium-90 Internal Radiation Therapy as Part of the Multimodality Treatment of Metastatic Colorectal Carcinoma 钇-90内放疗作为转移性结直肠癌多模式治疗的一部分

Onco Pub Date : 2021-12-11 DOI: 10.3390/onco1020015

M. D. Del Rosario, N. Abi-Jaoudeh, M. Cho, Z. Jutric, F. Dayyani

引用次数: 0

Decoding the Oncogenic Signals from the Long Non-Coding RNAs 从长非编码RNA中解码致癌信号

Onco Pub Date : 2021-12-10 DOI: 10.3390/onco1020014

Revathy Nadhan, D. Dhanasekaran

{"title":"Decoding the Oncogenic Signals from the Long Non-Coding RNAs","authors":"Revathy Nadhan, D. Dhanasekaran","doi":"10.3390/onco1020014","DOIUrl":"https://doi.org/10.3390/onco1020014","url":null,"abstract":"Cancer is one of the leading causes of death worldwide. Multifactorial etiology of cancer and tumor heterogeneity are the two most acute challenges in existing diagnostic and therapeutic strategies for cancer. An effective precision cancer medicine strategy to overcome these challenges requires a clear understanding of the transcriptomic landscape of cancer cells. Recent innovative breakthroughs in high-throughput sequencing technologies have identified the oncogenic or tumor-suppressor role of several long non-coding RNAs (lncRNAs). LncRNAs have been characterized as regulating various signaling cascades which are involved in the pathobiology of cancer. They modulate cancer cell survival, proliferation, metabolism, invasive metastasis, stemness, and therapy-resistance through their interactions with specific sets of proteins, miRNAs and other non-coding RNAs, mRNAs, or DNAs in cells. By virtue of their ability to regulate multiple sets of genes and their cognate signaling pathways, lncRNAs are emerging as potential candidates for diagnostic, prognostic, and therapeutic targets. This review is focused on providing insight into the mechanisms by which different lncRNAs play a critical role in cancer growth, and their potential role in cancer diagnosis, prognosis, and therapy.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45416332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Role of NK Cells in Cancer and Immunotherapy NK细胞在肿瘤和免疫治疗中的作用

Onco Pub Date : 2021-12-03 DOI: 10.3390/onco1020013

P. Vishwasrao, S. Hui, D. Smith, V. Khairnar

{"title":"Role of NK Cells in Cancer and Immunotherapy","authors":"P. Vishwasrao, S. Hui, D. Smith, V. Khairnar","doi":"10.3390/onco1020013","DOIUrl":"https://doi.org/10.3390/onco1020013","url":null,"abstract":"Increasing knowledge of cancer immunology has led to the design of therapies using immune cells directly or manipulating their activity, collectively termed immunotherapy. In the field of immuno-oncology, research on adaptive immune T cells has led to the development of CAR-T cells. Innate immune cells such as NK cells can also eliminate oncogenically transformed cells and regulate cells of the immune system. Considering NK cells as a live drug, numerous methods for the isolation and activation of NK cells have been shown to be clinically and therapeutically relevant. In such processes, various cytokines and antibodies present a source of stimulation of NK cells and enhance the efficacy of such treatments. The ex vivo expansion and activation of NK cells, along with genetic modification with CAR, enhance their antitumor activity. Recent preclinical studies have shown an antitumor effect through extracellular vesicles (EVs) derived from NK cells. Work with autologous NK cells has provided insights for clinical applications. In this review, we outline the recent advances of NK-cell-based immunotherapies, summarizing CAR-NK cells, BiKEs, and TriKEs as treatment options against cancer. This review also discusses the challenges of NK cell immunotherapy.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47513010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Non-Coding RNAs and Wnt/β-Catenin Signaling Pathway in Gastric Cancer: From EMT to Drug Resistance 癌症非编码RNA与Wnt/β-儿茶酚胺信号通路：从EMT到耐药性

Onco Pub Date : 2021-11-25 DOI: 10.3390/onco1020012

Bruno Takao Real Karia, Camila Albuquerque Pinto, C. Gigek, Fernanda Wisnieski, M. Arruda Cardoso Smith

{"title":"Non-Coding RNAs and Wnt/β-Catenin Signaling Pathway in Gastric Cancer: From EMT to Drug Resistance","authors":"Bruno Takao Real Karia, Camila Albuquerque Pinto, C. Gigek, Fernanda Wisnieski, M. Arruda Cardoso Smith","doi":"10.3390/onco1020012","DOIUrl":"https://doi.org/10.3390/onco1020012","url":null,"abstract":"Gastric cancer is one of the most common cancers and the third cause of cancer-related death worldwide. The treatment of GC patients improved due to advancements in surgery, radiotherapy and chemotherapy. However, the long-term survival rate of patients with gastric cancer remains around 20%. Thus, development of novel therapeutic approaches is of great interest, in order to reduce the need for mutilating surgeries and morbid adjuvant therapies. For many years, it was believed that the RNA was a mere intermediate molecule in the genetic information flow. However, during the past decades, with the advent of new sequencing technologies, it was revealed that non-coding RNAs play important roles in many different biological processes. The Wnt/β-catenin signaling pathway has been reported to regulate crucial events during neoplasic development, such as cell differentiation, proliferation, invasion, migration, apoptosis, and angiogenesis. In this review, we will focus on microRNAs and long non-coding RNAs that have been implicated in gastric cancer tumorigenesis via modulation of the Wnt/β-catenin signaling pathway, which provided some biomarkers to prognosis, diagnosis, and therapy.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44081593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

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